Trial of PRO1160 (GEN1160) in Relapsed or Refractory Non-Hodgkin Lymphoma (NHL) (PRO1160-001)

Launched by GENMAB · Jan 31, 2023

Keywords

ClinConnect Summary

This clinical trial, called PRO1160-001, is researching a new drug named PRO1160 for patients with advanced solid tumors or certain types of blood cancers, specifically Renal Cell Carcinoma (a type of kidney cancer), Nasopharyngeal Carcinoma (a cancer in the upper throat), and Non-Hodgkin Lymphoma (a type of blood cancer). The main goal of the study is to determine how safe the drug is and to find out the right dose to give to participants. The trial has two parts: the first part will focus on figuring out the best dosage, while the second part will check how well the drug works and its safety in treating these cancers.

To participate in this trial, individuals must have confirmed advanced cancer that cannot be surgically removed or has spread to other parts of the body. They should also have had previous treatments that didn't work for them. Participants need to provide a tumor sample and have a good performance status, meaning they are able to carry out daily activities with minimal assistance. Throughout the trial, participants will receive close monitoring for any side effects, and the information gained will help understand how to better treat these challenging cancers in the future. If you or a loved one are interested, it's important to discuss eligibility and details with your healthcare provider.

Gender

ALL

Eligibility criteria

• Dose Escalation: Key Inclusion Criteria:
• * All participants must have pathologically confirmed diagnosis of one of the following tumor types:
• • Metastatic RCC, including clear cell renal cell carcinoma (ccRCC) or papillary RCC
• • Metastatic or relapsed Epstein Barr virus (EBV)-associated NPC not amenable to further local therapies (EBV association may have been determined by testing on tumor tissue or peripheral blood)
• • Advanced (Stage III or IV) NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) requiring systemic therapy, and mantle cell lymphoma (MCL)
• * Participants must have relapsed or refractory disease following prior systemic therapies known to confer clinical benefit. At minimum, participants should have received the following therapies (unless deemed ineligible, refused by the participant, or not available in the region):
• • Participants with RCC must have received a minimum of one prior treatment regimen, and have received a tyrosine kinase inhibitor (TKI) and a programmed cell death (ligand) (\[PD\[L)\])-1 inhibitor
• • Participants with EBV-associated NPC must have received a minimum of one prior treatment regimen, which must include a platinum-based chemotherapy regimen
• • Participants with DLBCL must have received a minimum of 2 prior treatment regimens, including a multi-agent chemoimmunotherapy regimen given with curative intent (eg, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone \[R-CHOP\]), and participants must have received intensive salvage chemotherapy with hematopoietic stem cell transplant (HSCT) if considered eligible by the investigator
• • Participants with FL must have received a minimum of 2 prior treatment regimens, which must include a multi-agent chemoimmunotherapy regimen including an anti-CD20 agent
• • Participants with mantle cell lymphoma (MCL) must have received a minimum of 2 prior treatment regimens, which must include a multi-agent chemoimmunotherapy regimen including an anti-CD20 agent
• * Measurable disease at baseline:
• • Participants with RCC and NPC must have measurable disease as defined per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (Eisenhauer et al., 2009)
• • Participants with NHL must have measurable disease as defined by the Lugano Classification (Cheson et al., 2014)
• • Participants must be willing to provide a pre-treatment tumor specimen (archival or new tissue biopsy samples). If a new tissue biopsy is required, procedures more invasive than a core biopsy or significant risk procedures for which the procedure-associated absolute risk of mortality or major morbidity in the participant's clinical setting and specific institution is 2% or higher, should not be utilized.
• Dose Escalation Key Exclusion Criteria:
• • Prior treatment with anti-CD70 directed therapy
• • Prior therapy with an antibody-drug conjugate (ADC) with a topoisomerase 1 inhibitor payload
• • Prior allogeneic hematopoietic stem cell transplant (HSCT). Participants with prior autologous HSCT must have completed the procedure at least 100 days prior to the first dose of study drug.
• • Known active central nervous system metastases, including carcinomatous meningitis. Participants with brain metastases may participate provided the metastases have been treated and are stable for at least 4 weeks prior to the first dose of study drug, they have no new or enlarging brain metastases and have discontinued corticosteroids prescribed for symptoms associated with brain metastases for at least 7 days prior to the first dose of study drug. Participants with a history of brain metastases, suspected new brain metastases, or a diagnosis of RCC should have a magnetic resonance imaging (MRI) of the brain at screening.
• Expansion: Key Inclusion Criteria:
• • Has pathological diagnosis of DLBCL, not otherwise specified (NOS) as defined by the World Health Organization (WHO) 2016 classification including both de novo or histologically transformed.
• • Has relapsed or refractory disease with no available standard therapy or is not a candidate for available standard therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN1160 may be beneficial. Participant must have received at least 2 systemic treatment regimens including CD20-containing chemoimmunotherapy.
• * Has measurable disease according to the 2014 Lugano criteria (Cheson et al., 2014):
• • A fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan demonstrating positive lesion compatible with computed tomography (CT)- or MRI-defined anatomical tumor sites; AND
• • A CT scan (or MRI) with involvement of ≥ 1 measurable nodal lesion (long axis \> 1.5 centimeters (cm) and short axis \> 1.0 cm) and/or ≥ 1 measurable extranodal lesion (long axis \> 1.0 cm).
• • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• • Has a fresh biopsy (if clinically feasible and not considered as a high-risk procedure) or an archival tumor biopsy and submit to the central laboratory for CD70 assay
• • Has acceptable laboratory test results per protocol
• Expansion: Key Exclusion Criteria:
• • Primary central nervous system (CNS) tumor or known CNS involvement.
• * Has been exposed to any of the following prior therapies within the specified timeframes:
• • Received prior investigational CD70-targeting therapy, eg, CD70-directed chimeric antigen receptor T-cell (CAR-T) therapy, anti-CD70 monoclonal antibody (mAb), CD3 x CD70 bispecific monoclonal antibody (bsAb), or CD70 antibody-drug conjugate.
• • Autologous stem cell transplant within 60 days prior to the first dose of GEN1160.
• • Allogeneic stem cell transplant within 90 days prior to the first dose of GEN1160.
• • Chemotherapy within 2 weeks or major surgery within 4 weeks of the first dose of GEN1160.
• • Curative radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks prior to the first dose of GEN1160.
• • Treatment with an investigational drug within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of GEN1160 or currently receiving any other investigational agents.
• • Prior treatment with live, attenuated vaccines within 30 days prior to the first dose of GEN1160. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Experimental and/or nonauthorized coronavirus disease (SARS-CoV-2) vaccinations are not allowed.
• • Receiving immunosuppressive drugs or systemic corticosteroids such as prednisone at doses \> 25 milligrams (mg) daily or its equivalent within 14 days prior to the first dose of GEN1160.
• • History of symptomatic autoimmune disease (eg, rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis \[eg, Wegener's granulomatosis\]).
• * Has clinically significant cardiac disease, including:
• • Myocardial infarction within 6 months prior to the first dose of GEN1160, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III or IV), cardiac arrhythmia (Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0 Grade 2 or higher), or clinically significant electrocardiogram (ECG) abnormalities.
• • Screening 12-lead ECG showing a baseline QT interval as corrected by QTcF \> 480 milliseconds (msec).
• • Echocardiogram (ECHO) or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) \< 45%.
• • Has clinically significant toxicities from previous anticancer therapies that have not resolved to baseline levels or to Grade 1 or lower. Note, participants with ≤ Grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the trial.
• • Active graft versus host disease (GVHD) requiring immune suppression regardless of grade.
• • Note: Other protocol-defined Inclusion and Exclusion criteria may apply.